ADVERSE DRUG REACTIONS MAY CAUSE OVER 100,000 DEATHS AMONG HOSPITALIZED PATIENTS EACH YEAR

Study suggests adverse drug reactions
are among the top causes of death in U.S.

CHICAGO-Adverse
drug reactions (ADRs) in U.S. hospitals
may be responsible for more than 100,000 deaths nationwide each year,
making it one of the leading causes of death, according to an article in
the April 14 issue of The Journal of American Medical Association (JAMA).

Bruce
H. Pomeranz, M.D., Ph.D., and colleagues from the
University of Toronto, analyzed 39 studies of ADRs in the United States to
estimate the incidence of serious and fatal adverse drug reactions in
hospital patients. To obtain overall incidence rates of ADRs in
hospitalized patients, the researchers combined the incidence of ADRs in
the hospital and the incidence of ADRs causing admission to the hospital.

The
authors estimated that 2,216,000 hospital patients
experienced a serious ADR and 106,000 deaths were caused by ADRs in the
United States. This could account for 4.6 percent of all causes of recorded
death in 1994, making these reactions between the fourth and sixth leading
cause of death.

The
World Health Organization defines ADRs as any
noxious, unintended and undesired effect of a drug, which occurs at doses
used in humans for prophylaxis [prevention], diagnosis or therapy. The
authors define a serious ADR as one requiring hospitalization prolonging
hospitalization, or one that is permanently disabling or results in death.

The
researchers found no significant correlation between
ADR incidence and year the studies were conducted. They write: "This result
seems surprising since great changes have occurred over the last four
decades in U.S. hospitals that should have affected the incidence of ADRs.
Perhaps, while length of hospital stay is decreasing, the number of drugs
per day may be rising to compensate. Therefore, while the actual incidence
of ADRs has not changed over the last 32 years, the pattern of their
occurrence has, undoubtedly changed," the authors write.

The
authors determined that ADRs are one of the leading
causes of death by using the highest and lowest possible estimates. Using
the higher estimate placed ADRs as the fourth leading cause of death,
behind heart disease (743,460 deaths), cancer (529,904 deaths) and stroke
(150,108 deaths). Using the lower estimate placed ADRs as the sixth leading
cause of death behind those previously mentioned, as well as pulmonary
disease (101,077 deaths) and accidents (90,523 deaths). ADRs would then
rank ahead of pneumonia and diabetes.

The
authors conclude: "While our results must be viewed
with some circumspection because of the heterogeneity among the studies and
small biases in the sample, these data suggest that ADRs represent an
important clinical issue." (JAMA. 1998;279:1200-1205)

Editorial:
How Worried Should We Be?

In
an accompanying editorial in the April 15 JAMA, David
W. Bates, M.D., M.Sc., of Partners Healthcare Systems, and Brigham and
Women's Hospital, Boston, Mass., cautions that there are several concerns
about the way the study was done, although the authors adhered to the
generally accepted criteria for meta-analyses. "First, an inherent
limitation of meta-analysis is that combining the results of small,
heterogeneous studies does not necessarily bring one closer to truth,
particularly if the processes used to identify and to validate the presence
of the events were heterogeneous. Second, the hospitals studied are
probably not representative of hospitals at large. Such studies are more
likely to be conducted in academic, tertiary care hospitals; these
hospitals have sicker patients, and these patients have more ADRs. Another
issue is whether the sites of care sampled within the institutions were
representative of the institutions."

Dr.
Bates adds: "Nonetheless, these data are important,
and even if the true incidence of ADRs is somewhat lower than that reported
... it is still high, and much higher than generally recognized." (JAMA.
1998;279:1216-1217)